Initial Ca2 Research Articles

Inositol-1,4,5-Trisphosphate Receptor-1 and -3 and Ryanodine Receptor-3 May Increase Ooplasmic Ca2+ During Quail Egg Activation.

We previously reported that egg activation in Japanese quail is driven by two distinct types of intracellular Ca2+ ([Ca2+]i): transient elevations in [Ca2+]i induced by phospholipase Czeta 1 (PLCZ1) and long-lasting spiral-like Ca2+ oscillations by citrate synthase (CS) and aconitate hydratase 2 (ACO2). Although the blockade of inositol 1,4,5-trisphosphate receptors (ITPRs) before microinjections of PLCZ1, CS, and ACO2 cRNAs only prevented transient increases in [Ca2+]i, a microinjection of an agonist of ryanodine receptors (RYRs) induced spiral-like Ca2+ oscillations, indicating the involvement of both ITPRs and RYRs in these events. In this study, we investigated the isoforms of ITPRs and RYRs responsible for the expression of the two types of [Ca2+]i increases. RT-PCR and western blot analyses revealed that ITPR1, ITPR3, and RYR3 were expressed in ovulated eggs. These proteins were degraded 3 h after the microinjection of PLCZ1, CS, and ACO2 cRNAs, which is the time at which egg activation was complete. However, degradation of ITPR1 and ITPR3, but not RYR3, was initiated 30 min after a single injection of PLCZ1 cRNA, corresponding to the time of the initial Ca2+ wave termination. In contrast, RYR3 degradation was observed 3 h after the microinjection of CS and ACO2 cRNAs. These results indicate that ITPRs and RYR3 differentially mediate in creases in [Ca2+]i during egg activation in Japanese quail, and that downregulation of ITPRs and RYR3-mediated events terminate the initial Ca2+ wave and spiral-like Ca2+ oscillations, respectively.

Can ionized calcium levels and platelet counts used for estimating the prognosis of pediatric trauma patients admitted to the emergency surgery intensive care?

Injury is the leading cause of death for pediatric population older than 1 year of age and 95% of those deaths are from the low- and middle-income countries. Most of those injured pediatric patients are treated in general hospitals. In designated trauma centers, the outcomes of severely injured patients are better. Scoring systems used frequently in intensive care units (ICUs) to make triage easier and to estimate prognosis. However, some of the scores may require additional expensive and sometimes time consuming tests. The purpose of the present study was to compare the usefulness of several scoring systems with initial ionized calcium levels and platelet counts to predict prognosis of pediatric trauma patients admitted to the emergency surgery department. This retrospective study was performed at a tertiary university hospital. The patients' ages, genders, trauma etiologies, types of trauma, time of trauma, transport place (primary or secondary), duration of stay in the ICU and in the hospital, mortality rates, initial ionized calcium levels (Ca+2), initial platelet counts, and data of several trauma scores (GCS, RTS, ISS, TRISS, and PTS) were analyzed. One hundred and fourteen pediatric trauma patients were admitted to the ICU. The mean age was 77.8±54 months. Most of them were male, falls were the primary mechanism of injury, and head trauma was the most common pattern of injury. The mortality rate was 15.8%, and the admission values for Ca+2, platelet counts, GCS, RTS, TRISS, and PTS had been found higher for patients who survived, while ISS scores were higher for those who had died. It was found that pediatric patients admitted to the ICU were younger than 10 years, of whom most of them were male. Falls were the most common mechanism of injury, and head trauma was present in most of the pediatric patients admitted to the ICU. Initial Ca+2 levels and platelet counts can be used along with the trauma scoring systems in predicting mortality and overall survey regarding pediatric trauma patients.

Prognostic Significance of Preoperative and Postoperative CA 19-9 Normalization in Pancreatic Adenocarcinoma Treated with Neoadjuvant Therapy or Surgery First

Background: Normal(ization) of serum carbohydrate 19-9 (CA 19-9) before/after surgery has not been compared between patients with pancreatic adenocarcinoma (PDAC) treated with neoadjuvant therapy (NT) vs. surgery-first (SF). We hypothesized that postoperative normalized CA 19-9 is associated with dissimilar outcomes compared to normal(ization) before surgery. Methods: Clinicopathologic characteristics for patients with PDAC who underwent resection from July 2011 to October 2018 were abstracted from a prospective database. Patients with pre-/post-operative CA 19-9, total bilirubin <2mg/dL, and initial CA 19-9 >1 U/mL were included. Overall survival (OS) and recurrence-free survival (RFS) were compared among groups when stratified by pre-/post-operative CA 19-9. Results: In patients receiving NT (N = 171), normal pre-/post-operative CA19-9 (group “NT-1”) had the best median RFS and OS (26 and 77mo), followed by those who finally normalized after surgery (“NT-2,” 16 and 39mo). For SF patients (N = 57), normal pre-/post-operative CA19-9 (“SF-1”) had the best median RFS and OFS (28 and 57mo), followed by those who immediately normalized after resection (“SF-2,” 18 and 49mo). Groups “NT-3” (n=36) and “SF-3” (n=11) with elevated CA 19-9 both before and after resection had the worst median RFS and OS durations (Figure 1). Conclusion: While a normal(ized) postoperative CA 19-9 may result in similar survival as preoperative normal(ization), postoperative normalization failed to occur in 28.9% of SF patients, despite careful selection. Thus, NT should be considered in patients presenting with elevated CA 19-9. If considering surgery-first, the ideal patients are those with normal pre-operative CA 19-9.

Initial carbonate weathering is linked with vegetation development along a 127-year glacial retreat chronosequence in the subtropical high mountainous Hailuogou region (SW China)

AimsThe retreat of glaciers is exposing new terrains to primary plant succession around the globe. To improve the understanding of vegetation development along a glacier retreat chronosequence, we (i) evaluated a possible link between base metal (Ca, Mg, K, Na) supply and vegetation establishment, (ii) determined the rates of the establishment of soil and plant base metal stocks, and (iii) estimated the size of the main base metal fluxes.MethodsWe determined base metal stocks in the soil organic layer, the mineral topsoil (0–10 cm), and in leaves/needles, trunk, bark, branches and roots of the dominating shrub and tree species and estimated fluxes of atmospheric deposition, plant uptake and leaching losses along the 127-yr Hailuogou chronosequence.ResultsTotal ecosystem Ca and Mg stocks decreased along the chronosequence, while those of K and Na were unrelated with ecosystem age. Fortyfour and 30% of the initial stocks of Ca and Mg, respectively, were leached during the first 47 years, at rates of 130 ± 10.6 g m−2 year−1 Ca and 35 ± 3.1 g m−2 year−1 Mg. The organic layer accumulated at a mean rate of 288 g m−2 year−1 providing a bioavailable base metal stock, which was especially important for K cycling.ConclusionsWe suggest that the initial high Ca bioavailability because of a moderately alkaline soil pH and carbonate depletion in 47 years, together with the dissolution of easily-weatherable silicates providing enough Mg and K to the pioneer vegetation, contributed to the establishment of the mature forest in ca. 80 years.

A Novel Alternative Methods for Decalcification of Water Resources Using Green Agro-Ashes.

The strategic idea in this work was to increase pH values by employing natural alkali sources (i.e., HCO3− and CO32−) from four tested agro-ashes as an alternative to chemicals (i.e., lime or soda ash). The considerable proportion of carbonates and bicarbonates in the investigated ash products had remarkable features, making them viable resources. All ash materials showed a significant ability for Ca ion elimination at high initial Ca ion concentrations. A slight quantity of ash (10 g/L) was sufficient for usage on very hard water contents up to 3000 ppm. Finally, the tested agro-ash was free of cost. Furthermore, unlike other conventional precipitants, such as NaOH, Ca(OH)2, NaHCO3, Na2CO3, and CaO, they are cost effective and ecologically sustainable. There is no need to employ any additional chemicals or modify the agro-ash materials throughout the treatment process. The benefits of the manufactured ash were assessed using a SWOT analysis.

Effects of dietary supplementation of endo-(1,4)-β-xylanase in plant-based diets on growth performance, hindgut microbial diversity, and blood chemistry in large on-growing African catfish (Clarias gariepinus)

ABSTRACT The study aimed to investigate the impacts of dietary supplementation of endo-(1,4)-β-xylanase in high plant-ingredient diets in on-growing African catfish (Clarias gariepinus). A high plant-ingredient basal diet was supplemented with exogenous xylanase at 0 (Control diet), 100, 150, and 200 ppm, and fed to on-growing (initial weight ca 500 g) fish for a duration of 91 days. Growth parameters, fillet proximate composition, hindgut microbial diversity, hindgut short-chain fatty acid concentration, and blood chemistry parameters were monitored. There were no effects on growth parameters, fillet proximate composition, hindgut short-chain fatty acid concentration, and blood chemistry parameters. Dietary xylanase supplementation caused a significant shift in hindgut microbial diversity, where the 200 ppm treatment showed significantly lower Shannon diversity (2.15 ± 0.13) than the control (2.78 ± 0.21). The significantly lower microbial diversity indicates that enzyme supplementation selectively benefitted certain microbial populations in the hindgut, presumably through the release of prebiotic compounds during non-starch polysaccharide hydrolysis. It is concluded that dietary xylanase supplementation can significantly impact hindgut microbial communities in on-growing African catfish, and it is recommended that future work investigate whether dietary xylanase supplementation can benefit aquaculture production performance in younger fish.

Time-Dependent Image Restoration of Low-SNR Live-Cell Ca2 Fluorescence Microscopy Data.

Live-cell Ca fluorescence microscopy is a cornerstone of cellular signaling analysis and imaging. The demand for high spatial and temporal imaging resolution is, however, intrinsically linked to a low signal-to-noise ratio (SNR) of the acquired spatio-temporal image data, which impedes on the subsequent image analysis. Advanced deconvolution and image restoration algorithms can partly mitigate the corresponding problems but are usually defined only for static images. Frame-by-frame application to spatio-temporal image data neglects inter-frame contextual relationships and temporal consistency of the imaged biological processes. Here, we propose a variational approach to time-dependent image restoration built on entropy-based regularization specifically suited to process low- and lowest-SNR fluorescence microscopy data. The advantage of the presented approach is demonstrated by means of four datasets: synthetic data for in-depth evaluation of the algorithm behavior; two datasets acquired for analysis of initial Ca microdomains in T-cells; finally, to illustrate the transferability of the methodical concept to different applications, one dataset depicting spontaneous Ca signaling in jGCaMP7b-expressing astrocytes. To foster re-use and reproducibility, the source code is made publicly available.

Magnetic Resonance Guided Stereotactic Ablative Radiation Therapy vs. Chemoradiation for Borderline and Locally Advanced Pancreatic Cancer: Single Institution Overall Survival Comparison

Several academic institutions have investigated stereotactic MR guided adaptive radiation therapy (SMART) to safely dose escalate for locally advanced and borderline resectable pancreatic cancer with initial favorable toxicity and survival outcomes. In 2018 our institution began to evaluate SMART on trial in borderline and locally advanced patients. We previously presented toxicity outcomes for standard fractionated chemoradiation (chemoRT) and SMART groups with acute grade 3+ GI toxicity in 28% vs 11% (P = 0.18) and late toxicity 43% vs 36% (P = 0.77). The purpose of this abstract was to compare overall survival (OS) between chemoRT and SMART.In this IRB approved analysis, we retrospectively reviewed 115 consecutive patients from 2017-2020 with locally advanced or borderline resectable pancreatic cancer who were treated with neoadjuvant radiation therapy. Initially all patients received chemoRT to a dose of 50.4 Gy in 28 fractions. In September 2018 we began to investigate SMART (50Gy in 5 fractions) for these patients. OS was evaluated by Kaplan-Meier and log-rank test. Univariate and multivariate analysis was also performed on multiple treatment variables.Of the patients included, 30 received chemoRT and 85 received SMART. Median follow up for the chemoRT group was 32.8 months and for SMART was 14.9 months from last day of RT. Groups did not have significant differences in age, gender, tumor location, or initial CA 19-9. Pancreatectomy was performed in 13.3% vs 18.8% of patients in chemoRT and SMART groups. Per NCCN.1.2021 staging in the chemoRT group 33.3% were borderline (BL), 50% were locally advanced (LA), and 16.7% medically unresectable (MU) as compared to 24.7% BL, 49.4% LA, and 25.9% MU in the SMART group. Mean months of neoadjuvant chemo was slightly higher in the SMART group at 3.6 vs 2.3 months. Patients in the chemoRT arm were 36.7% African American vs 15.3% in the SMART group. When evaluated using Kaplan-Meier and log-rank test there was no difference in OS between groups (P = 0.95). Median OS from last day of RT in chemoRT and SMART groups was 10.7 vs 12.1 months. On univariate and multivariate analyses pancreatectomy was associated with improved OS, and both N2 disease at diagnosis and poor performance status (ECOG 2+) were associated with worse OS.Dose escalated SMART for locally advanced, borderline, and medically inoperable pancreatic cancer shows similar OS to standard fractionated chemoRT at a median 14.9 month follow up in our single institution analysis. With similar toxicity and OS between treatment modalities, SMART may be preferred due to the single week treatment course in a disease with overall very poor prognosis.

Fine property-tuning through Ca content control in a facile synthesis of glasses-based self-setting injectable hydrogel

Self-setting injectable composite hydrogels are promising materials in tissue engineering. In this study a facile synthetic approach was designed based on traditional sol–gel method to produce particulate calcium aluminosilicate-type glasses, which were then formulated with potassium alginate to form a self-setting injectable hydrogel. In order to control the setting-time and mechanical properties of the composite materials, a series of samples were produced with different starting chemical composition. The change in chemical composition and morphology of the glass particles in response to varying initial Ca2+ content were further elucidated by a combination of EM, XRF and NMR spectroscopy, revealing that the binary aluminosilicate glass was preferably formed when low Ca content (<20%) was used in the formulation. At higher Ca content (>30%), calcium aluminosilicates were predominantly formed due to the change in the type of zeolite precursor formed during the low temperature nucleation process in the sol–gel approach. It was also found the hardening times of the alginate gels was positively correlated to the mole ratio of Ca/Al due to high acid resistance of high coordination number Al species. For hydrogels made with glass particle additions, the mechanical strengths were also positively correlated with the Ca/Al ratio for all formulations.

Dentin remineralization in acidic solution without initial calcium phosphate ions via poly(amido amine) and calcium phosphate nanocomposites after fluid challenges.

A previous study showed that the combination of poly(amido amine) (PAMAM) and rechargeable composites with nanoparticles of amorphous calcium phosphate (NACP) induced dentin remineralization in an acidic solution with no initial calcium (Ca) and phosphate (P) ions, mimicking the oral condition of individuals with dry mouths. However, the frequent fluid challenge in the oral cavity may decrease the remineralization capacity. Therefore, the objective of the present study was to investigate the remineralization efficacy on dentin in an acid solution via PAMAM + NACP after fluid challenges for the first time. The NACP nanocomposite was stored in a pH 4 solution for 77days to exhaust its Ca and P ions and then recharged. Demineralized dentin samples were divided into four groups: (1) control dentin, (2) dentin coated with PAMAM, (3) dentin with recharged NACP composite, and (4) dentin with PAMAM + recharged NACP. PAMAM-coated dentin was shaken in phosphate-buffered saline for 77days to desorb PAMAM from dentin. Samples were treated in pH 4 lactic acid with no initial Ca and P ions for 42days. After 77days of fluid challenge, PAMAM failed to prevent dentin demineralization in lactic acid. The recharged NACP nanocomposite raised the pH to above 6.5 and re-released more than 6.0 and 4.0mmol/L Ca and P ions daily, respectively, which inhibited further demineralization. In contrast, the PAMAM + NACP combined method induced great dentin remineralization and restored the dentin microhardness to 0.54 ± 0.04 GPa, which approached that of sound dentin (P = 0.426, P > 0.05). The PAMAM + NACP combination achieved dentin remineralization in an acid solution with no initial Ca and P ions, even after severe fluid challenges. The novel PAMAM + NACP has a strong and sustained remineralization capability to inhibit secondary caries, even for individuals with dry mouths.

P–279 Effect of Ca2+ ionophore A23187 (calcymicin) on fertilization rates, embryo development and pregnancy in human assisted reproduction cycles

Abstract Study question Does Calcymicin improve reproductive outcomes of ICSI cycles in cases of fertilization failure and/or embryo blockage indications? Summary answer The application of the Calcymicin after ICSI improves reproductive outcomes, especially in cases with clinical indication of fertilization failure. What is known already According to the bibliography, deficiencies in the oocyte activation process frequently lead to failed ICSI cycles, and these can be corrected by increasing initial levels of calcium (Ca2+) in the oocyte using assisted oocyte activation techniques (AOA), such as the use of Ca2+ ionophores. Ca2+ Ionophores have been shown to trigger an initial Ca2+ spike in the ooplasm that activates Ca2+/Calmodulin dependent protein kinase II, which initiates the cascade of cellular events leading to oocyte activation. Previous results suggest that Ca2+ ionophore treatment can give live offspring after failed ICSI cycles. Study design, size, duration 270 oocytes collected from 17 patients who presented cycles with low fertilization rates and/or embryo blockage or poor quality embryos (according to ASEBIR’s embryo classification criteria) were retrospectively analyzed. Oocytes were divided into two groups, a control group that underwent conventional IVF/ICSI and another group that underwent an ICSI cycle with AOA. Study groups were defined according to clinical indications and subgroups according to AOA or control. All data were collected from 2017 until 2020. Participants/materials, setting, methods Among the 270 oocytes of the study sample, 142 belonged to the control group and 128 belonged to the AOA group. The AOA group oocytes were activated for 15 minutes immediately after ICSI using a prepared solution containing the Ca2+ ionophore A23187, CultActive© (Gynemed, Germany). Fertilization rate and type, blastocyst formation rate, blastocyst quality, embryo kinetics, and pregnancy rates were analyzed, all of them were compared to FIV/ICSI cycles without oocyte activation (control group). Main results and the role of chance In the analyses of the whole sample of oocytes, the AOA treatment gave a fertilization rate of 72.5%, which was significantly higher compared to 53.8% of the control cycles (p = 0.002). Good quality blastocysts and pregnancy rates were also significantly higher than the control (p = 0.01). In the group with an indication of fertilization failure, a significantly higher fertilization rate was recorded compared to the control (65% and 33%, respectively). A higher rate of abnormal embryos with three pronuclei was also found compared to the control (p &amp;lt; 0.001). There were no significant differences in blastocyst formation rates, quality, or embryo kinetics (p &amp;gt; 0.05). In the group with an indication of embryo blockage/poor embryo quality, a significantly higher rate of good quality blastocysts and lower blastulation time were recorded compared to the control (p &amp;lt; 0.05). Limitations, reasons for caution The safety of the AOA technique with Ca2+ ionophore has not been fully demonstrated. In our study, none of the newborns had malformations, and gestational weeks and birth weights were normal. However, further studies on the safety of this technique are needed to implement it routinely in human reproduction clinics. Wider implications of the findings: According to these findings, an increase in the initial levels of calcium in the oocyte through the application of the Ca2+ ionophore A23187 after ICSI improves the results of failed assisted reproduction cycles, especially in the case of those diagnosed with fertility failure, which is a clear indication for AOA. Trial registration number Not applicable

Signal strength controls the rate of polarization within CTLs during killing.

Cytotoxic T lymphocytes (CTLs) are key effector cells in the immune response against viruses and cancers, killing targets with high precision. Target cell recognition by CTL triggers rapid polarization of intracellular organelles toward the synapse formed with the target cell, delivering cytolytic granules to the immune synapse. Single amino acid changes within peptides binding MHC class I (pMHCs) are sufficient to modulate the degree of killing, but exactly how this impacts the choreography of centrosome polarization and granule delivery to the target cell remains poorly characterized. Here we use 4D imaging and find that the pathways orchestrating killing within CTL are conserved irrespective of the signal strength. However, the rate of initiation along these pathways varies with signal strength. We find that increased strength of signal leads to an increased proportion of CTLs with prolonged dwell times, initial Ca2+ fluxes, centrosome docking, and granule polarization. Hence, TCR signal strength modulates the rate but not organization of effector CTL responses.

Graphitic carbon nitride nanosheet as an excellent compound for the adsorption of calcium and magnesium ions: theoretical and experimental studies

In this work, the removal of calcium (Ca2+) and magnesium (Mg2+) ions were studied using graphitic carbon nitride (g-C3N4) nanosheet as an adsorbent from aqueous solutions. In experimental studies, the effects of various adsorption parameters were investigated by batch method culture including pH, initial Ca2+ and Mg2+ concentrations, temperature, time, and adsorbent mass. The best results were obtained at pH=8.50, 0.05 g of g-C3N4, 90 min, 10 ppm of ion concentration, 23.80 mg g-1 of maximum adsorption capacity for Ca2+, and pH=9, 0.05 g of g-C3N4, 60 min, 15 ppm of ion concentration, 40.00 mg g-1 maximum adsorption capacity for Mg2+ ion. The adsorption of calcium and magnesium ions obeyed the Langmuir model on adsorbent. In theoretical study, g-C3N4 nanosheet as an interesting material was studied by first-principle calculation using the Quantum Espresso package. The Ca2+ and Mg2+ ions were located at different positions on g-C3N4 nanosheet to obtain the stable configuration. The Eads, HOMO, LUMO, Eg, band structure, DOS and PDOS plots were investigated at stable configuration of g-C3N4 nanosheet. The adsorption energy (Eads) was calculated -15.55 and -26.24 eV for Ca2+ and Mg2+ ions, respectively. Further, the results indicated that Mg2+can be located at the center of the porous g-C3N4 nanosheet, which the adsorption of Mg2+ on surface of g-C3N4 nanosheet was stronger than that of Ca2+ ion. Theoretical and experimental data confirmed each other’s findings. The adsorption of Ca2+ and Mg2+ ions was shown to be simple, high-yield, eco-friendly, and economical performance from aqueous solutions using g-C3N4 nanosheet

A six years longitudinal cohort study on the changes in bone density and bone quality up to peak bone mass in adolescent idiopathic scoliosis (AIS) with and without 2 years of Calcium and Vit-D supplementation.

Adolescent idiopathic scoliosis (AIS) is associated with osteopenia which could persist into adulthood affecting attainment of Peak Bone Mass thus resulting in osteoporosis in late adulthood. We previously reported a randomized double-blinded placebo-controlled trial(the Cal study) showing significant bone health improvement with 2-year calcium(Ca)+Vit-D supplementation for AIS girls. This study addressed the important issue whether bone health improvement from the initial 2-year Ca+Vit-D supplementation could persist as subjects approached towards Peak Bone Mass at 6-year ie after 4-year of supplement discontinuation. This was an extension of the Cal study on AIS girls (11-14 years old, mean age=12.9 years, Tanner stage<IV) with femoral neck aBMD Z-score<0 and Cobb angle≥15∘. 330 subjects were randomized to Group1(placebo), Group2(600mgCa+400-IU-Vit-D3/day) or Group3(600mgCa+800-IU-Vit-D3/day) for 2-year supplementation after which supplementation was stopped. Investigations at baseline, 2-year and 6-year included High-resolution Peripheral Quantitative Computed Tomography(HR-pQCT) at distal radius and Dual Energy X-ray Absorptiometry(DXA) at both hips. 270(81.8%) subjects completed 2-year supplementation when changes in left femoral neck aBMD, trabecular vBMD, Trabecular BV/TV, Trabecular Number and Trabecular Separation indicated significant bone health improvement with Ca+Vit-D supplementation(p<0.05). At 6-year(mean age=19.2 years), no between-group difference on bone parameters was noted except increase in Cortical Thickness being greater only in Group3 than in Group1. After 4-year supplement discontinuation, the treatment effect from the initial 2-year supplementation mostly dissipated indicating the need of continued supplementation in AIS girls to sustain therapeutic improvement on bone health as subjects approach towards Peak Bone Mass.

No Observed Adverse Effects on Health Were Detected in Adult Beagle Dogs When Fed a High-Calcium Diet for 40 Weeks.

Simple SummaryCalcium (Ca) is an essential mineral that plays a vital role in many bodily functions. There is evidence that high levels of dietary Ca for puppies and growing dogs can result in adverse growth and health effects, with certain breeds and dog size categories being most susceptible, for example, large breed sizes or beagles. Until recently, little was known about the health consequences of high Ca diets to adult dog, however, a study in the large sized breed Labrador retriever found no adverse health consequences when feeding diets containing levels of Ca near maximum levels set by pet food regulators (2.5 g per 100 g dry matter) for 40 weeks. This current study fed a similar high Ca diet to adult beagles, a medium sized breed for 40 weeks and monitored the dogs’ health using an extensive suite of health parameters. All dogs remained healthy and did not display any clinically relevant signs of adverse health relating to diet at any point during or following completion of the study.The implications of long-term high calcium (Ca) intake are well documented in growing dogs and in adult dogs of large breed size, however, the consequences on other breeds and breed sizes are yet to be determined. Eighteen neutered adult beagles, nine males and nine females aged 1.4–4.4 years, were randomized to control or test diets providing in g∙4184 kJ−1 (1000 kcal−1): 1.44 and 7.19 total Ca balanced with 1.05 and 4.25 total phosphorus, respectively, for 40 weeks. Health parameters, ultrasound scans, radiographs, glomerular filtration rate, and mineral balance were measured at eight-week intervals. All dogs remained healthy with no measured evidence of orthopedic, urinary, or renal disease. The test diet resulted in a 5.2 fold increase in fecal Ca excretion. Apparent Ca digestibility (%) and Ca balance (g/d) did not significantly (p > 0.05) change from baseline in the test diet group, although dogs displayed a positive Ca balance (maximum at week 8, 1.11 g/d with 95% CI (0.41, 1.80)) before a neutral Ca balance was restored at week 32. Despite an initial positive Ca balance, we can conclude that no measurable adverse health effects were observed as a result of the test diet fed in this study in beagles over a period of 40 weeks.

Impaired Ca2+ signaling due to hepatic steatosis mediates hepatic insulin resistance in Alström syndrome mice that is reversed by GLP-1 analog treatment.

Ca2+ signaling plays a critical role in the regulation of hepatic metabolism by hormones including insulin. Changes in cytoplasmic Ca2+ regulate synthesis and posttranslational modification of key signaling proteins in the insulin pathways. Emerging evidence suggests that hepatocyte intracellular Ca2+ signaling is altered in lipid-loaded liver cells isolated from obese rodent models. The mechanisms of altered Ca2+-insulin and insulin-Ca2+ signaling pathways in obesity remain poorly understood. Here, we show that the kinetics of insulin-initiated intracellular (initial) Ca2+ release from endoplasmic reticulum is significantly impaired in steatotic hepatocytes from obese Alström syndrome mice. Furthermore, exenatide, a glucagon-like peptide-1 (GLP-1) analog, reversed lipid-induced inhibition of intracellular Ca2+ release kinetics in steatotic hepatocytes, without affecting the total content of intracellular Ca2+ released. Exenatide reversed the lipid-induced inhibition of intracellular Ca2+ release, at least partially, via lipid reduction in hepatocytes, which then restored hormone-regulated cytoplasmic Ca2+ signaling and insulin sensitivity. This data provides additional evidence for the important role of Ca2+ signaling pathways in obesity-associated impaired hepatic lipid homeostasis and insulin signaling. It also highlights a potential advantage of GLP-1 analogs when used to treat type 2 diabetes associated with hepatic steatosis.

Initial Ca 125 Value as a Predictive Marker for High-grade Serous Ovarian Cancer.

To determine the relevance between the cut-off level of cancer antigen 125 (CA 125) level and long-term prognosis in high-grade serous ovarian cancer (HGSCs). Observational study. Departments of Oncology, Medeniyet University Goztepe Education and Research Hospital, and Kartal Lutfi Kirdar Education and Research Hospital, Istanbul, Turkey, from January 2017 to June 2019. Medical records of 230 women with HGSC were reviewed randomly from two Oncology Clinics. Descriptive analysis and CA 125 marker levels were evaluated with five years of disease-free survival rate (DFS) and overall survival rate (OS). Patients were divided into groups of high and low initial CA 125 levels (cut-off ≥385U/ml). The ability of initial serum CA 125 levels in predicting the presence of marker-recurrence of ovarian cancer were analysed using ROC (Receiver operating characteristics) curve analysis. Statistically significant predictive value of initial CA 125 level was calculated as 385U/ml (p=0.008). The 5-year DFS of high and low CA 125 levels for all stages in HGSC was statistically significant (p<0.001). The sub-group analysis demonstrated that the significant survival difference was especially in FIGO stage III. Patients with HGSC <385 U/ml had a significantly improved 5-year DFS and OS rates within stage III disease: 5-year DFS (p = 0.008) and 5-year OS (p = 0.004) according to the stratification of CA 125 level. Initial CA 125 level appeared to be of beneficial clinical predictive value for HGSC. Key Words:Initial CA 125, Tumor marker, High-grade serous ovarian cancer, Disease-free survival, Overall survival, Predictive value.

Synchronous anodic oxidation-cathodic precipitation strategy for efficient phosphonate wastes mineralization and recovery of phosphorus in the form of hydroxyapatite

• Electrochemical “oxidation-precipitation” system can recover phosphorus from phosphonates. • Phosphorus was electrochemically recovered in the form of hydroxyapatite (HAP) within 120 min. • BDD( OH) led to the fastest orth-P yield, medium TOC attenuation and slowest nitrate formation. • The HAP formation proceeded via brushite, octacalcium phosphate and amorphous calcium phosphate. To make up the gap of wasted phosphonates being too much as pollutants and phosphorus being too little as a natural resource, electrochemical “oxidation-precipitation” system was rationally developed to recover phosphorus with simultaneous mineralization of ethylenediamine tetra(methylene phosphonic acid) (EDTMP), a typical phosphonate. In this process, BDD( OH) was the primary oxidative species for EDTMP degradation, which led to the bond cleavage in the sequence of C-N, C-P and C-C. Increasing current density from 3 to 30 mA cm −2 improved the mineralization efficiency of EDTMP from 14% to 72% within 120 min, accompanying 65–95% of EDTMP conversion to orth-P. With the presence of 50 mg L −1 Ca 2+ , 21–83% of phosphorus was recovered as insoluble calcium phosphate at the cathode surface. High initial Ca 2+ concentration favored the phosphorus recovery, whereas it was negatively influenced with the presence of Mg 2+ and HCO 3 – . In addition, phosphorus recovery was negligibly affected by solution pH in the range of 3.0 to 12.0 because the locally alkaline condition was well maintained at the cathode surface. Phosphorus was electrochemically recovered mainly in the form of thermodynamically most stable hydroxyapatite, which proceeded via the formation of brushite, octacalcium phosphate, and amorphous calcium phosphate with Δ[Ca]/Δ[P] molar ratio increasing from 1.0 to 1.67. Based on the results of phosphorus recovery from the real wastewater, we envision that this synchronous anodic oxidation-cathodic precipitation process can be applied as an environmentally compatible and feasible strategy for phosphorus recovery from the phosphonate wastewaters.

A general framework to model the fate of trace elements in anaerobic digestion environments

Due to the multiplicity of biogeochemical processes taking place in anaerobic digestion (AD) systems and limitations of the available analytical techniques, assessing the bioavailability of trace elements (TEs) is challenging. Determination of TE speciation can be facilitated by developing a mathematical model able to consider the physicochemical processes affecting TEs dynamics. A modeling framework based on anaerobic digestion model no 1 (ADM1) has been proposed to predict the biogeochemical fate TEs in AD environments. In particular, the model considers the TE adsorption–desorption reactions with biomass, inerts and mineral precipitates, as well as TE precipitation/dissolution, complexation reactions and biodegradation processes. The developed model was integrated numerically, and numerical simulations have been run to investigate the model behavior. The simulation scenarios predicted the effect of (i) organic matter concentration, (ii) initial TEs concentrations, (iii) initial Ca–Mg concentrations, (iv) initial EDTA concentration, and (v) change in TE binding site density, on cumulative methane production and TE speciation. Finally, experimental data from a real case continuous AD system have been compared to the model predictions. The results prove that this modelling framework can be applied to various AD operations and may also serve as a basis to develop a model-predictive TE dosing strategy.

CO2 Sequestration in the Production of Portland Cement Mortars with Calcium Carbonate Additions

The paper presents the obtention and characterization of Portland cement mortars with limestone filler and nano-calcite additions. The nano-calcite was obtained by the injection of CO2 in a nano-Ca(OH)2 suspension. The resulted nano-CaCO3 presents different morphologies, i.e., polyhedral and needle like crystals, depending on the initial Ca(OH)2 concentration of the suspension. The formation of calcium carbonate in suspensions was confirmed by X-ray diffraction (XRD), complex thermal analysis (DTA-TG), scanning electron microscopy (SEM) and transmission electron microscopy (TEM and HRTEM). This demonstrates the viability of this method to successfully sequestrate CO2 in cement-based materials. The use of this type of nano-CaCO3 in mortar formulations based on PC does not adversely modify the initial and final setting time of cements; for all studied pastes, the setting time decreases with increase of calcium carbonate content (irrespective of the particle size). Specific hydrated phases formed by Portland cement hydration were observed in all mortars, with limestone filler additions or nano-CaCO3, irrespective of curing time. The hardened mortars with calcium carbonate additions (in adequate amounts) can reach the same mechanical strengths as reference (Portland cement mortar). The addition of nano-CaCO3 in the raw mix increases the mechanical strengths, especially at shorter hardening periods (3 days).